Myocardial studies with 99mTc@labeled phosphate agents were obtained in 20 patients without demonstrable cardiovascular disease, 24patients with unstable arteriosclerotic heart digease (ASHD) without acute infarction, and sixpatients with myocardiopathy. The patientswithout cardiovascular disease showed no localization of tracer; the patients with unstable ASHDand without acute infarction showed nonfocal

ill-defined accumulation of tracer; and the patients with myocardiopathy showed diffuse accumulation of tracer throughout the confinesof an enlarged cardiac outline. Careful evaluation of both the distribution and intensity ofthe activity, in conjunction with the clinical picture, allows differentiation among these diseaseprocesses. Since ischemic areas around infarctedtissue may show increased activity, the value ofthis technique for sizing acute myocardial infarction may be limited.

Bonte reported that eemTc@stannouspyrophosphatelocalizes in dog myocardium after experimentallyproduced myocardial infarction (1 ) . Investigationsin humans showed positive myocardial images in 15patients with acute transmural myocardial infarction(2) . Of these patients 13 gave positive studies 3—7days after the initial episode. Electrocardiograms(ECG) correlated well with the localization of theinfarct. Two patients with arteriosclerotic heart disease (ASHD) showed questionably increased activity in the region of the left ventricle (2) . Acutesubendocardial infarction has also been documentedwith this technique (3). Willerson et al have reported that of 55 patients admitted for chest painwho did not evolve ECG or enzyme evidence ofmyocardial infarction, none showed positive localiza

tion of tracer to the myocardium (4) . In anotherstudy, Willerson et al reported on 202 patients admitted to their coronary care unit with chest painof varying origins (5) . Of these, 101 did not developclinical or electrocardiographic evidence of acutemyocardial infarction and 92 had negative myocardial scintigrams. Seven of the remaining nine patientshad “unstableangina pectoris―and a faint, but definitely positive myocardial scintigram (5) . The present investigation was undertaken to assess the possible cardiac uptake of radiophosphate in patientswith no demonstrable cardiac disease, with arteriosclerotic heart disease, and with myocardiopathy.

MATERIALS AND METHODS

Fifteen millicuries of either eemTc_stannous polyphosphate (New England Nuclear Corp., North Bitlerica, Mass.) or oemTc@pyrophosphate (TechneScanPYP Kit, Mallinckrodt/Nuclear, St. Louis, Mo.)was administered intravenously to each patient. Thetracer was prepared according to the manufacturer's

Received May 24, 1975; revision accepted Oct. 22, 1975.For reprints contact: Louis A. Perez, Dept. of Nuclear

Medicine, Norwalk Hospital, 24 Stevens St., Norwalk, Conn.06856.

FIG. 1. Normalheart(Group1).Radioactivityis notincreasedin vicinity of heart.

241Volume 17, Number 4

jnm/DIAGNDBTIC NUCLEAR MEDICINE

LOCALIZATION OF MYOCARDIAL DISORDERS

OTHER THAN INFARCTION WITH

99mTCLABELED PHOSPHATE AGENTS

LouisA. Perez, David B. Hayt, and Leonard M. Freeman

Misericordia Hospital Medical Centerand the Albert Einstein College of Medicine, Yeshiva University, Bronx, New York

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TABLE 1.PATIENTSWITh ARTERIOSCLEROTICHEARTDISEASEANDNOACUTEINFARCTIONPa

tlentNo.AgeSexInterval

betweenanginol episode

and imaging(days)Dischargediagnosis ECG findingsHigh

estSGOTHigh

utCPKHigh

estLDHScintigram177F7tSR

with frequent APCs2155205

PEREZ, HAYT, AND FREEMAN

instructions and used within 3 hr of preparation. At era peak set at 140 keV with a 20% window. The90 mm and again at 4 hr after injection, left an- records were obtained with Polaroid and 35-mm film.tenor, left anterior oblique, and left lateral scinti- Informed consent was obtained from all patients.grams of the upper thorax were obtained. Using a They were divided into three groups:Searle Radiographics Pho/Gamma III HP scintilla- Group 1. Patients without evidence of cardiotion camera, a high-resolution 140-keV collimator vascular disease.was centered at the point of maximal cardiac pulsa- Group 2. Patients with arteriosclerotic hearttion for each view. Three hundred thousand counts disease without acute infarction.were accumulated for each scintigram with the cam- Group 3. Patients with myocardiopathy.

Mild increased activity at inferioraspect of left ventricle

30 55 305 Mild increased activity at apexof left ventricle

30 70 360 Mild increased activity at inferior aspect of left ventricle

15 75 220 Moderate increased ill-definedactivity at anterior left yentricle

36 120 350 Mild increased activity at apexof left ventricle

22 55 250 Moderate increased activity atinferior surface of left ventricle

38 110 330 ModerateIncreasedactivityatmedial border of left ventricle

20 60 200 Mild increasedactivityatmedial border of left ventridc

80 40 280 Mild increased activity through.out left ventricular contour

33 60 185 Mildincreasedactivitythroughout left ventricular contour

24 205 350 Moderate increased activity atapex of left ventricle

23 1t5 390 Moderate increased activity atanterior left ventricle

20 60 200 Mild increased activity at inferior surface of left ventricle

34 60 350 Mildincreasedactivityat antenor left ventricle

51 175 245 Moderate increased activity atinferior surface of left yentricle

56 110 390 Mild increased activity atanterior left ventricle

28 115 200 Moderateincreasedactivityatmedial inferior border ofright ventricle

40 140 295 Mild increasedactivityat antenor left ventricle

30 100 330 Mildincreasedactivityat Inferior surface of left yen.tricle

14 70 260 Mild increased activity at antenor and inferior left ventide

28 80 160 Mild increased activity at Inferior surface of left ventricle

24 95 240 Moderateincreasedactivityatapex of left ventricle

27 165 290 Mild increased activity at apexand anterior left ventricle

24 65 340 Mild increased activity at apexof left ventricle

Old anterior wall myocardiolinfarct-—ag. indeterminate

Nonspecific ST & T wavechanges. Old anteroseptalinfarct. Atrial fibrillationwith rare ectopic beats

NonspecificST & T wavechanges

NonspecifIc ST & T wavechanges

Nonspecific ST& T wavechanges

Old inferior wall myocordialinfarct—ageindeterminate

Old inferior wall myocardial

infarct—age indeterminate

Left ventricular hypertrophy

Nonspecific ST & T wavechanges. intraventricularconduction defect

NonspecificST & I wavechanges

Old anteroseptal myocardial

infarct—ageindeterminateNonspecificST & T wave

changesNonspecific ST & T wave

changesNonspecificST & I wave

changes

Left bundle branch block

tSR, occasional SVBs

Right bundle branch block

Nonspecific ST & T wavechanges

Old inferior wall myocardialinfarct—age indeterminate

Nonspecific ST & T wavechanges

Nonspecific ST & T wavechanges

Left ventricular hypertrophy

Old anteroseptal myocardialinfarct—ageindeterminate

ASHD with cardiomegaly.

CAstomach,S/P subtotalgastredtomy

2 62 M 2 ASHD—unstableangina

3 66 M 6 ASHD with cardiomegaly.CAlung.S/P rightupper lobectomy

4 36 M 2 Acute pulmonary thromboemboli

S 51 F 7 Hypercholesterolemia

6 56 M 2 ASHD, diabetes

7 50 F 3 ASHD with cardiomegaly.hypertension

8 72 F 3 ASHDwithunstableangina

9 65 F 8 ASHD with cardiomegaly.CAcervix

10 87 M 2 ASHD with unstable angina, CA prostate

11 42 F 8 CAbreast,S/P radicalmastectomy.diabetes,hypercholesterolemia,hypothyroidism

12 60 M 3 ASHD with unstable angina, cardiomegaly

13 83 M 10 CA prostate

14 75 F 3 ASHD with unstable angina

15 55 M 20 ASHD. diabetes, CA colon

16 59 F 3 ASHD with unstable angina. cardiomegaly.acute pulmonarythromboemboli

17 76 F 5 CA colon, ASHD. diabetes

18 71 F 3 ASHD with unstable angina

19 72 M 7 ASHD. CA prostate. S/Pprostatectomy

20 48 M 3 ASHD, cardlamegaly,anxiety reaction

21 86 F 6 ASHD. cardiomegaly. CA

breast bilateral22 70 F 4 ASHD with unstable angina

23 59 F 2 ASHD, cardiomegaly. hy.pertension. diabetes

24 54 F 3 ASHD with unstable angina,deep thrombophlebitisin right lower extremity

. Normal valus: SOOT 7—40 units; CPK 0—130 units; LDH 150—400 units.

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Pa High High.HightientestestestNo.

Age Sex Chestpain Condition ECGfindings SGOTCPKLDH Scintigram

1 50 M None 80 120 330

DIAGNOSTICNUCLEARMEDICINE

gina! episode who were not admitted for suspectedacute myocardial infarction. Acute infarction wasexcluded in Group 2 by serial ECGs, serum enzymestudies, and subsequent clinical course.

Group 3. Myocardiopathy. Six patients were studied: all were men, with an age range of 50—70years.A strong history of alcoholic intake was present infour cases. The diagnosis of myocardiopathy wasmade on clinical grounds.

RESULTS

Group 1. No patient had any history of significantcardiac disturbance and physical examination didnot disclose cardiac disease. Electrocardiogramswere all normal, and the highest SGOT, CPK, andLDH values were within normal limits. No myocardial activity was found in 19 of the 20 patientsstudied (Fig. 1) . The exception, a 31-year-oldwoman without confirmable cardiac disease, showedincreased tracer uptake at about the inferior andapical border of the left ventricle. It was not superimposed breast activity, which in this patient waslocalized anterior to the chest wall by a lateral scmtigram. The myocardial activity was confined to thethoracic cavity and did not move with the breast onthe lateral scintigrams. The patient has no knownprimary or metastatic malignant disease. We have

no explanation for this scintigraphic finding.Group 2 (Table 1). All 24 patients had confirma

tory history and physical findings for ASHD. Eachwas studied 2—20 days after an anginal episode. Allshowed ill-defined faint-to-moderate activity in theregion of the anterior or inferior aspect of the leftventricle (Fig. 2). Serial ECG and serum enzymes

-f

——,,@:1k.

FIG.2. Unstablearterioscleroticheartdisease(Group2).Notemoderate ill-defined nonfocal increased radioactivity in vicinity ofleft ventricle.

The Group I patients were studied as part of anexamination for routine bone imaging. They wereall informed that the images of the heart were beingobtained as part of a clinical investigation.

Group 1. No evidence of cardiovascular disease.Twenty patients were studied: 10 men and 10women. The age range was 18—69years. All hadhistory, physical examination, and electrocardiograms. Serum-enzyme determinations included glutamic-oxaloacetic transaminase (SGOT), lactic dehydrogenase (LDH), and creatine phosphokinase(CPK).

Group 2. Arteriosclerotic heart disease withoutacute infarcion. Twenty-four patients were studied:

10 men and 14 women. The age range was 36—87years. These patients all had angina and some hadprevious myocardial infarction as indicated by dcctrocardiograms. This group is actually composedof two subgroups. Approximately one-half were admitted with chest pain and the suspicion of acutemyocardial infarction, and the other half were patients with arteriosclerotic disease and a recent an

TABLE 2. PATiENTS WITH MYOCARDIOPATHY

AlcoholicmyocardiopathyLeft

ventricularhypertrophyFaint

increased activity throughout enlarged cardiac

silhouette252MNoneAlcoholic

myocardiopathyleftbundle

branchblock40140360Faintincreasedactivity through

out enlarged cardiacsilhouette359MNoneAlcoholic

myocardiopathyleftventricular

hypertrophy3524240Moderateincreased activity

throughout enlarged cardiacsilhouette470MNoneAlcoholic

myocardiopathyLeftventricular

hypertrophy6070300Faintincreased activity through

out enlarged cardiacsilhouette577MNoneIdiopathic

myocardiopathyAVblockand

incompleteright bundlebranch block5971270Marked

increased activitythroughout enlarged cardiac

silhouette655MNoneIdiopathic

myocardiopathyLeftventricular

hypertrophy70110300No increasedactivity

Volume 17, Number 4 243

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Clinical diagnosis Distribution of activity Intensity of activity

Normal None None

PEREZ, HAYT, AND FREEMAN

excluded acute myocardial infarction. For those patients who previously had acute myocardial infarction, clinical history and electrocardiogram datingcould not pinpoint the time of the previous infarction. However, it seemed clear that an intervalgreater than 3 weeks had existed between the previous infarction and the subsequent imaging.

Group 3 (Table 2). The diagnosis of myocardiopathy was made on clinical grounds. Five of the sixpatients were volunteers from the cardiac clinic andone was an occult case discovered incidentally at thetime of bone imaging for an unrelated disorder. Noneof the patients was hypertensive or in cardiac decompensation at the time of imaging. Four patientshad confirmatory history and physical findings foralcoholic myocardiopathy. They all presented without chest pain and with normal SGOT, CPK, andLDH enzyme values. Electrocardiography showedleft ventricular hypertrophy in three patients. Thefour patients with alcoholic myocardiopathy showedfaint-to-moderate diffuse activity throughout themarkedly enlarged cardiac silhouette (Fig. 3) . Oneof the two patients with idiopathic myocardiopathyshowed similar findings.

DISCUSSION

Bonte et al studied patients with arterioscleroticheart disease without acute infarction and foundactivity in the region of the left ventricle. Myocardialactivity with 9OmTc.labeled phosphate agents neednot indicate acute myocardial infarction. Myocardialactivity has been detected in one out of 20 normalpatients and in 24 out of 24 patients with arteriosclerotic heart disease but without acute infarction.Since confusion could arise if poor labeling of thephosphate caused an increase in free technetium andpersistent activity in the cardiac blood pool, we cornpared the 90-mm scintigrams with others obtainedat 4 hr. The same abnormal myocardial activity wasobserved on the 4-hr studies in all patients who were

positive at 90 mm, although the activity was somewhat less intense. The O9mTc4abeled phosphate wastested for free technetium at the time of administration, using instant thin-layer chromatography withsilica-gel medium and acetone as solvent (6,7) . Atno time was more than 12% of free technetiumfound, and usually only 5% was present; this iscomparable to results obtained elsewhere (6,7) . Inaddition, no activity was detected in the thyroid orstomach area of any patient.

We have no reason to believe that the kinetics ofthe technetium-labeled polyphosphate and pyrophosphate in our patients was in any way different fromthat reported (7) . It seems unreasonable to assumethat increased and persistent blood-pool activity, dueto altered plasma binding or inappropriate labelingwith a phosphate, has occurred in all our patientswith arteriosclerotic heart disease and myocardiopathy. This is especially unlikely in that 19 normalpatients did not show myocardial activity. Moreover,some of the normal patients were injected from thesame batch of radiopharmaceutical as were the patients who showed myocardial activity. Persistentblood-pool activity could also be accentuated in patients with chronic renal failure, but of those studiednone had chronic renal failure and only one was incardiac decompensation. Another potential pitfall

FIG.3. Myocardiopathy(Group3).Notefaintdiffuseincreasedradioactivity throughout markedly enlarged cardiac silhouette.

TABLE 3. SCINTIGRAPHIC OBSERVATIONS IN MYOCARDIAL ABNORMALITIES USING99mTc4@BELEDPHOSPHATES

Acute myocardial infarct Focal, corresponding to distribution ofoccluded vessel

Moderate to marked

ASHD without acute infarct (stable) None None

ASHD without acute infarct (unstable),

recent anginal episodeIll-defined, in region of left ventricle Mild to moderate

Myocardiopathy Diffuse, involves entire radiographic cardiac contour

Usually mild to moderate, occasionallymarked

244 JOURNAL OF NUCLEAR MEDICINE

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DIAGNOSTIC NUCLEAR MEDICINE

lated by the difficulties in infarct diagnosis encountered by the standard methods. An extension of thisreasoning suggests the exciting possibility that theabnormal uptake in our patients with arterioscleroticheart disease might conceivably represent areas ofsubclinical infarction, not confirmable by standarddiagnostic tests. Further investigative work shouldhelp to confirm or refute this possibility. As withother radionuclide imaging studies, the specificity ofthe procedure is always enhanced by evaluating theresults in conjunction with other clinical considerations. In addition, careful assessment of the intensityand distribution of the abnormal activity should helpto differentiate the entities of acute infarction, arteriosclerotic heart disease without acute infarction,and myocardiopathy (Table 3, Fig. 4) . We emphasize the relatively unstable status of the Group 2patients. All had recent angina, but no evidence ofacute infarction was present.

Myocardial imaging with oomTc@labeledphosphateis a simple safe noninvasive technique which may beuseful to establish the presence or absence of myocardial infarction. Whether the localization of tracerdetectable by a camera indicates only frank infarctionor may also include areas of simple ischemia stillremains to be determined. This situation may besimilar to that of labeled tetracycline in ischemicmyocardium (1 1 ) . Attempts have been made to sizeacute myocardial infarction in patients using similar methods ( 12) . If it should turn out, however, thatthe scintigram also signals simple ischemia, the estimate of “infarctsize―may be too generous.

REFERENCES

1. BONTE FJ, PARKEY RW, GRAHAM KD, et al: A newmethod for radionuclide imaging of myocardial infarcts.Radiology 110: 473—474,1974

2. PARKEYRW, BONTEFJ, MEYERSL, et al: A newmethod for radionuclide imaging of acute myocardial in.farction in humans. Circulation 50: 540—546,1974

3. WILLERSON JT, PARKEY RW, BONTE FJ, et al: Acutesubendocardial myocardial infarction in patients. Circulation51: 436—441,1975

4. WILLERSONJT, PARKEYRW, BONTEFJ, Ct al: Technetium 99m stannous pyrophosphate myocardial imaging inthe diagnosis of acute myocardial infarction in patients.Circulation 49—50:Suppl No 3, 4, 1974

5. WILLERSONJT, PARKEYRW, BONTEFJ, et al : Technetium stannous pyrophosphate myocardial scintigrams inpatients with chest pain of varying etiology. Circulation 51:1046—1052,1975

6. BILLINGHURSTMW: Chromatographicquality controlof mmTc-Iabeled compounds. I Nucl Med 14: 793—797,1973

7. KRISHNAMURTHYGT, HUEBOrrERRJ, WALSHCF,et al: Kinetics of ‘@mTc-labeled pyrophosphate and poly

phosphate in man. I Nucl Med 16: 109—115, 1975

8. SERAFINIAN, RASKINMM, ZAND LC, et al: Radionuclide breast scanning in carcinoma of the breast. I NuclMed 14:1149—1152,1974

FIG.4. Bycomparisonofscintigraphicpatternsof myocardialactivity, various disease processes can generally be distinguished.

is breast localization of phosphate agents, describedby several investigators (8) . The lateral scintigramis particularly helpful in such situations.

Bonte et al postulated that myocardial infarctioninduces cellular influx of calcium ions with localization in the mitochondria near the hydroxyapatitecrystal (1 ) . Thus, in myocardial ischemia withoutinfarction, the phosphate tracer may be showing thisintracellular flux of calcium ions from the sarcoplasmic reticulum to the mitochondria (9) . Thesechanges may occur early in myocardial ischemia andhave been demonstrated before standard clinicalsigns of overt cardiac failure appeared (9) . Similarly, these intracellular changes associated with thepreclinical stages of cardiac failure may occur inarteriosclerotic heart disease without overt infarction. It is well known that the “diagnosisof acutemyocardial infarction depends on inferential clinicaland laboratory data, including the occurrence ofchest pain, sequential electrocardiographic changes,and altered pattern in serum enzyme activity―(10).Much of the enthusiasm for 99mTc@labeledphosphateor tetracycline in myocardial imaging has been stimu

Volume 17, Number 4 245

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PEREZ, HAYT, AND FREEMAN

9. CHIDSEYCA : Calcium metabolismin the normal andf@i1ing heart. In The Myocardium: Failure and Infarction,Braunwald E, ed, New York, Hospital Practice Publishing,1974,pp 37—47

10. HOLMAN LB, LESCH M, ZWEIMAN FG, et al: Detection and sizing of myocardial infarcts with technetium99m (Sn) tetracycline. N Engi I Med 291 : 159—163,1974

11. POE ND, RoBINsoN GD: Relation between bloodflow and uptake of labeled tetracycline in ischemic myocardium. Clin Res 23: No. 2, 1, 125A, 1975

12. HARRIS RA, PARKEYRW, BONTE FJ, et al: Sizingacute myocardial infarction in patients utilizing technetiumstannous pyrophosphate myocardial scintigrams. Clin Res23: No. 1,3A, 1975

Dallas, TexasJune 8—11,1976

J

246 JOURNAL OF NUCLtAR MEDICINE

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Members and nonmembers of the Society of Nuclear Medicine are invited to attend the 23rd An

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1976;17:241-246.J Nucl Med.   Louis A. Perez, David B. Hayt and Leonard M. Freeman  Phosphate Agents

Tc-Labeled99mLocalization of Myocardial Disorders other than Infarction with

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